A study of lipid peroxidation (LPO) and related functions in rat and chick liver microsomes metabolizing CCl4 under dietrary conditions known to influence the mixed-function oxidase system and microsome lipid composition is proposed. Preliminary studies have shown that one of the major proteins in the molecular weight range of the P-450 cytochromes which is induced in liver microsomes by phenobarbvital (PB) disappears within two hours after administering CCl4. Since PB induction is known to enhance CCl4 toxicity, we purified and fractionated the P-450 cytochromes from PB-induced liver microsomes and observed that only the fraction containing the PB-induced P-450 cytochrome which corresponds to the band which disappears in liver microsomes of CCl4-treated animals is capable of producing the trichloromethyl radical (CCl3) from CCl4 in reconstituted mixed function oxidase systems. On the other hand, major bands in the P-450 molecular weight range which are induced by Beta-naphthoflavone are decreased only slightly even as long as 4 hrs after treatment with the same dose of CC14. The results indicate that the relative amounts of different P-450 cytochromes in liver microsomes may be an important factor in determining the degree of toxicity of a given dose of CCl4. Since dietary fat influences both the amount of P-450 cytochromes present in liver in liver microsomes and the degreee of unsaturation of microsomal lipids, the studies described are designed to investigate the relationships between a) the forms of the P-450 cytochromes which are characteristic for the dietary conditions described; b) the capacity of the various forms of P-450 cytochromes to produce CCl3 in vitro; c) the amount of LPO catalyzed by microsomes metabolizing CCl4 in vitro; d) diene conjugation in vivo; e) the intensity of CCl3 formed in the liver of intact animals; f) the influence of dietary antioxidants, and g) the amount of lowering liver glutathione peroxidase activity on liver damage, P-450 loss, diene conjugation and CCl3 formation in vivo will be assayed. Objective: to determine how LPO relates to liver injury caused by CCl4.